FB2024_03 , released April 23, 2024
Gene: Dmel\fwe
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General Information
Symbol
Dmel\fwe
Species
D. melanogaster
Name
flower
Annotation Symbol
CG6151
Feature Type
FlyBase ID
FBgn0261722
Gene Model Status
Stock Availability
Gene Summary
flower (fwe) encodes a transmembrane protein with different isoforms expressed in 'loser' and in 'winner' cells to mediate win/lose decisions in cell competition and neuronal culling during development and ageing. [Date last reviewed: 2019-02-28] (FlyBase Gene Snapshot)
Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-43
RefSeq locus
NT_037436 REGION:15810081..15816410
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (15 terms)
Molecular Function (1 term)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from direct assay
Terms Based on Predictions or Assertions (0 terms)
Biological Process (11 terms)
Terms Based on Experimental Evidence (10 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN001779219
Cellular Component (3 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
located_in plasma membrane
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
located_in membrane
inferred from electronic annotation with InterPro:IPR019365
Protein Family (UniProt)
Belongs to the calcium channel flower family. (Q95T12)
Protein Signatures (InterPro)
Summaries
Gene Snapshot
flower (fwe) encodes a transmembrane protein with different isoforms expressed in 'loser' and in 'winner' cells to mediate win/lose decisions in cell competition and neuronal culling during development and ageing. [Date last reviewed: 2019-02-28]
Gene Group (FlyBase)
UNCLASSIFIED CALCIUM CHANNEL-FORMING SUBUNITS -
This group comprises calcium channel-forming subunits that do not classify under other groups in FlyBase.
Protein Function (UniProtKB)
Transmembrane protein which mediates synaptic endocytosis, fitness-based cell culling, neuronal culling, morphogen gradient scaling, and calcium transport (PubMed:20627080, PubMed:23810538, PubMed:25601460, PubMed:28011160, PubMed:33300871, PubMed:35301437). Regulates synaptic endocytosis and hence couples exo- with endocytosis (PubMed:19737521, PubMed:28414717, PubMed:29288152, PubMed:33300871). Controls two major modes of synaptic vesicle (SV) endocytosis in the synaptic boutons of neuromuscular junctions (NMJs); Ca(2+) channel-independent Clathrin-mediated endocytosis (CME) in response to mild stimulation, and Ca(2+) channel-dependent activity-dependent bulk endocytosis (ADBE) in response to strong stimulation (PubMed:28414717, PubMed:33300871). Functions in ADBE and subsequent SV reformation from bulk endosomes by initiating Ca(2+) channel-dependent phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) compartmentalization in synaptic boutons (PubMed:28414717, PubMed:33300871). There it acts at the periactive zone to provide the low Ca(2+) levels required to initiate Calcineurin activation and upregulate PtdIns(4,5)P2 (PubMed:33300871). Conversely PtdIns(4,5)P2 enhances fwe Ca(2+) channel-activity, establishing a positive feedback loop that induces PtdIns(4,5)P2 microdomain at the periactive zone (PubMed:33300871). These microdomains trigger bulk membrane invagination (i.e. ADBE) by triggering actin polymerization while also promoting localization of fwe to bulk endosomes, thereby removing the ADBE trigger to reduce endocytosis and prevent excess membrane uptake (PubMed:33300871). PtdIns(4,5)P2 then promotes SV reformation from the bulk endosomes, to coordinate ADBE and subsequent SV reformation (PubMed:33300871). Different combinations of the flower isoforms at the cell membrane are also required for the identification and elimination of suboptimal or supernumerary cells during development, regeneration, and adulthood (PubMed:20627080, PubMed:20951347, PubMed:23810538, PubMed:25601460, PubMed:28011160, PubMed:30590040). Required for the recognition and elimination of unfit cells in the developing wing during cell competition (PubMed:20627080). Also required for efficient identification and elimination of injured, damaged and/or dysfunctional neurons during regeneration of the adult brain (PubMed:25754635, PubMed:30590040). In the developing pupal retina, mediates the elimination of unwanted postmitotic neurons, including supernumerary photoreceptor neurons that form at the periphery of the retina and are contained within incomplete ommatidia units (PubMed:23810538). Downstream of the flower fitness fingerprints, cells identified as unwanted or unfit are eliminated via apoptosis through the expression of ahuizotl (azot) (PubMed:25601460, PubMed:30590040). However, the cells marked for elimination by the flower isoforms only undergo apoptosis if additional thresholds are met; (1) their neighboring fit/healthy cells express different levels of the fwe isoforms, and (2) the levels of the protective signal SPARC expressed by the loser or unwanted cells are unable to inhibit caspase activation (PubMed:20627080, PubMed:20951347, PubMed:23810538). These additional thresholds for flower-mediated apoptosis, allows useful cells to recover from transient and limited stress before they are unnecessarily eliminated (PubMed:20951347). Functions with dally and magu in a mechanism of scaling, which utilises apoptosis to ensure that the dpp morphogen gradient, which mediates organ growth, remains proportional to the size of the growing wing (PubMed:35301437). In this mechanism, fwe represses dally- and Magu-dependent activity in expanding the gradient, and dally/Magu inhibits fwe-dependent apoptosis to keep cell death rate low (PubMed:35301437). When the levels of these different proteins are optimally regulated the gradient correctly scales with organ growth but when this fails, fwe-mediated apoptosis is activated to trim the developing tissue to match the correct size of the gradient (PubMed:35301437).
(UniProt, Q95T12)
Summary (Interactive Fly)

Transmembrane protein - expressed in 'loser' cells to mediate win/lose decisions in cell competition by means of differentially expressed isoforms

Gene Model and Products
Number of Transcripts
3
Number of Unique Polypeptides
3

Please see the JBrowse view of Dmel\fwe for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry Q95T12)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Low-frequency RNA-Seq exon junction(s) not annotated.

Gene model reviewed during 5.45

Gene model reviewed during 5.55

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0075542
1342
194
FBtr0075541
3020
192
FBtr0075543
2364
157
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0075297
20.6
194
6.43
FBpp0075296
20.6
192
5.11
FBpp0075298
17.2
157
8.47
Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Crossreferences
InterPro - A database of protein families, domains and functional sites
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\fwe using the Feature Mapper tool.

External Data
Crossreferences
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.94

Transcript Expression
Polypeptide Expression
No Assay Recorded
Stage
Tissue/Position (including subcellular localization)
Reference
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
motor neuron

Comment: presynaptically localized

mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

fwe exhibits an isoform-dependent expression pattern. fwe-PA (fweUbi) is expressed ubiquitiously in the wing disc. In the pupal retina, at 44 hours APF, fwe-PA is expressed broadly, including in the neuronal layer. fwe-PC (fweLose-A) is expressed in all retinal neurons, while fwe-PB (fweLoseB) is expressed in ommatidia at the periphery of the retina, where photoreceptor neurons are undergoing programmed cell death.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in plasma membrane
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\fwe in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 20 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 39 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of fwe
Transgenic constructs containing regulatory region of fwe
Aberrations (Deficiencies and Duplications) ( 2 )
Inferred from experimentation ( 2 )
Gene disrupted in
Gene partially disrupted in
Inferred from location ( 0 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (1)
12 of 14
Yes
Yes
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (1)
12 of 14
Yes
Yes
Mus musculus (laboratory mouse) (1)
11 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (1)
4 of 13
Yes
Yes
Danio rerio (Zebrafish) (1)
12 of 14
Yes
Yes
Caenorhabditis elegans (Nematode, roundworm) (1)
13 of 14
Yes
Yes
Anopheles gambiae (African malaria mosquito) (1)
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (0)
Saccharomyces cerevisiae (Brewer's yeast) (1)
1 of 13
Yes
Yes
Schizosaccharomyces pombe (Fission yeast) (1)
1 of 12
Yes
Yes
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:fwe. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 1 )
    Allele
    Disease
    Interaction
    References
    Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    DO term
    Complementation?
    Transgene?
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Other Interaction Browsers

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    RNA-protein
    Physical Interaction
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    esyN Network Key:
    Suppression
    Enhancement
    Other Interaction Browsers

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Linkouts
    DroID - A comprehensive database of gene and protein interactions.
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    External Data
    Linkouts
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3L
    Recombination map
    3-43
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    72A1-72A1
    Limits computationally determined from genome sequence between P{EP}Tfb2EP572 and P{lacW}thj5C8&P{PZ}Mbs03802
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (18)
    Genomic Clones (18)
     

    Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

    cDNA Clones (102)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequenced
    BDGP DGC clones
    Other clones
    Drosophila Genomics Resource Center cDNA clones

    For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

    cDNA Clones, End Sequenced (ESTs)
    RNAi and Array Information
    Linkouts
    DRSC - Results frm RNAi screens
    Antibody Information
    Laboratory Generated Antibodies
    Commercially Available Antibodies
     
    Cell Line Information
    Publicly Available Cell Lines
     
      Other Stable Cell Lines
       
        Other Comments

        flower mutants display normal exocytosis but impaired endocytosis.

        Area matching Drosophila ESTS AA441468 and AA142226 (inverted). Sequence similarity to C. elegans protein Z66496.

        Relationship to Other Genes
        Source for database merge of

        Source for merge of: flower CG6151

        Source for merge of: CG6151 anon-WO0118547.242

        Additional comments

        Source for merge of CG6151 anon-WO0118547.242 was sequence comparison ( date:051113 ).

        Nomenclature History
        Source for database identify of

        Source for identity of: fwe flower

        Nomenclature comments
        Etymology

        This gene is called 'flower' due to the mutant phenotype where numerous extra synaptic boutons are generated, often in small clusters that are 'flowery in nature'.

        Synonyms and Secondary IDs (8)
        Reported As
        Secondary FlyBase IDs
        • FBgn0259121
        • FBgn0036533
        • FBgn0062151
        Datasets (0)
        Study focus (0)
        Experimental Role
        Project
        Project Type
        Title
        Study result (0)
        Result
        Result Type
        Title
        External Crossreferences and Linkouts ( 38 )
        Sequence Crossreferences
        NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
        GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
        GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
        RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
        UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
        UniProt/Swiss-Prot - Manually annotated and reviewed records of protein sequence and functional information
        Other crossreferences
        AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
        BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
        DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
        EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
        FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
        InterPro - A database of protein families, domains and functional sites
        KEGG Genes - Molecular building blocks of life in the genomic space.
        MARRVEL_MODEL - MARRVEL (model organism gene)
        Linkouts
        Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
        DroID - A comprehensive database of gene and protein interactions.
        DRSC - Results frm RNAi screens
        FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
        FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
        Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
        Flygut - An atlas of the Drosophila adult midgut
        iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
        Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
        MIST (protein-protein) - An integrated Molecular Interaction Database
        References (102)